Method for producing 2-chloro-5-chloromethyl-1,3-thiazol

Abstract

The invention relates to a method for producing 2-chloro-5-chloromethyl-1,3-thiazol from compounds of formula (I), wherein X means Cl, -OR, -SR or NR2, R being H or a suitable protective group; Y means H or Cl and Z means Cl or O, the compounds of formula (I) having at most one double bond between C* and C'' or between C'' and Z, on the condition that the bond between C'' and Z is a double bond when Z is the same as O and a single bond when Z is the same as Cl; with the following intermediate stage: A1) reacting 2,3-dichloropropanal with rhodanide and acetalising to 3-chloro-1,1-dialkoxy-2-isothiocyanato-propane or a2) reacting 2,3-dichloropropanal with thiourea to form a mixture of the hydrochlorides of the compounds N-[[5-(2-aminothiazol)yl]methyl]thiourea and [5-(2-aminothiazol)yl]methylthioformamidine and splitting to obtain the corresponding thiol or amine or b) reacting a compound of formula (I) wherein X means OR, SR or NR2, Y means clorine and Z means oxygen with thiourea to produce the compound of formula (V), or c) reacting a compound of formula (I), wherein X means OR, SR or NR2, Y means chlorine and Z means oxygen with ammoniumdithiocarbamate or ammoniumthiocarbamate, to produce the compound (VIa) or (VIb); d) converting 1,2,3-trichloropropane to the corresponding thiazolidine and then dehydrogenating or e) converting 1,3-dichloro-prop-1-ene to the corresponding epoxide and then reacting said epoxide with thiourea (e1) or ammoniumdithiocarbamate or ammoniumthiocarbamate (e2).

We claim:  
     
       1. A process for the preparation of 2-chloro-5-chloromethyl-1,3-thiazole, which comprises reacting 1,3-dichloro-1-propene with an oxidizing agent selected from peroxy acids, an acid/H 2 O 2  mixture, inorganic or organic peroxides or hydroperoxides in a solvent selected from nitriles or chlorinated hydrocarbons to convert it to the corresponding epoxide, which is 
       a 1 ) converted directly to 2-amino-5-chloromethyl-1,3-thiazole by thiourea in a suitable solvent selected from C 1 -C 6 -carboxylic acids, halogenated aliphatic or aromatic hydrocarbons, ethers, ketones, amides, sulfoxides or nitriles and is then converted to 2-chloro-5-chloromethyl-1,3-thiazole by Sandmeyer diazotization in the presence of inorganic or organic nitrites in HCl or in mixtures of HCl and an organic polar solvent, optionally in the presence of a copper halide catalyst or  
       a 2 ) is first converted to the compound of the formula (I)                    
       wherein R is C 1 -C 6  alkyl, by thiourea in the presence of an alcohol ROH,  
       wherein R is C 1 -C 6  alkyl, optionally in combination with a solvent selected from the group of C 1 -C 6 -carboxylic acids, halogenated aliphatic or aromatic hydrocarbons, ethers, ketones, amides, sulfoxides or nitriles and is then converted to a compound of the formula (II)                    
       wherein R is C 1 -C 6  alkyl, by Sandmeyer diazotization, whereupon 2-chloro-5-chloromethyl-1,3-thiazole is obtained after ether cleavage and chlorination.  
     
     
       2. The process as claimed in  claim 1 , wherein, in variant a 2 , the ether cleavage and chlorination take place in a single step which involves substituting the C 1 -C 6  alkoxyl group of the compounds of the formula II directly by a chlorine atom by reaction with POCl, or an acetyl chloride, optionally in combination with a Lewis acid, or with dry HCl in combination with a Lewis acid. 
     
     
       3. The process as claimed in  claim 1 , wherein, in variant a 2 , the C 1 -C 6 -alkoxyl group of the compounds of the formula II is substituted by chlorine by reaction with thionyl chloride.